Major depressive disorder (MDD) is one of the most common mental disorders and is associated with significant personal and societal costs [1]. Given the high rates of MDD onset and recurrence, research is needed to better understand the bio-psychosocial mechanisms that contribute vulnerability to depression. Although existing research has evaluated various physiological, affective, and environmental risk factors for MDD, much prior work has evaluated risk factors in isolation without considering the dynamic relationships among these processes in conferring risk for depression. This proposal seeks to evaluate physiological markers of the occurrence of daily stressors and affective reactivity to stressors, mutable and potent vulnerabilities for MDD onset and recurrence, among individuals at high risk for depression. The proposed project is designed to 1) evaluate physiological re-activities as predictors of daily stress generation and affective reactivity to stressors among lat adolescents at risk for future MDD, 2) examine daily stress generation as a mechanism linking physiological re-activities and daily affective reactivity, as well as subsequent depressive symptoms, and 3) explore sex differences in these processes as contributors to women's greater vulnerability to MDD using multiple units of analysis. Given that late adolescence is a period in which there are high rates of first onset and recurrence of MDD [2], as well as significant increases in stressful life events, participants in the proposed study will be undergraduate students with a history of major or sub-threshold depression, an important group at risk for future episodes of MDD [3]. Participants will complete a baseline evaluation of psychophysiological reactivity (via respiratory sinus arrhythmia and pre-ejection period) to a laboratory-induced stress challenge, as well as self-report symptoms of depression and life events that occurred in the prior six weeks (followed by a life events interview). Participants the will complete daily diary assessments for two weeks (14 diaries) evaluating life stressors and positive and negative affect in response to stressors, allowing for idiographic (within-subject) measurement of variations in stress and affect. At a follow-up assessment one month later, participants again will complete the life events questionnaire and interview, and measure of depressive symptoms. Consistent with the NIMH Strategic Objectives (2.3), this multi-method, micro-longitudinal study proposes to evaluate the relationships among physiological, environmental, and affective processes in vulnerability to depression measured using multiple units of analysis, which has the potential to elucidate the mechanisms through which these vulnerabilities confer risk for depression to better identify individuals at risk and inform novel nd personalized prevention and intervention programs for depression.